JC virus infection in colorectal neoplasia that develops after liver transplantation.
OBJECTIVE
Liver transplant recepients (LTRs) have an increased risk of colorectal neoplasia. The mechanism responsible for this is unknown. JCV encodes for TAg and has been implicated in colorectal carcinogenesis. We hypothesized that the use of immunosuppression in LTRs facilitates activation of JCV and is responsible for the increased risk of neoplasia.


METHODS
JCV TAg DNA and protein expression were determined in normal colonic epithelium (n = 15) and adenomatous polyps (n = 26) from LTRs and compared with tissue samples from control patients (normal colon, n = 21; adenomas, n = 40). Apoptosis and proliferation were determined by M30 and Ki-67 immunoreactivity, respectively.


RESULTS
JCV TAg DNA was found in 10 of 15 (67%) of normal colonic mucosa from LTRs compared with 5 of 21 (24%) of control normal mucosa (P = 0.025). JCV TAg DNA was detected in 16 of 26 (62%) of the adenomas from LTRs and in 20 of 40 (50%) of control adenomas. JCV TAg protein was expressed in 13 of 26 (50%) adenomas from LTRs versus 2 of 40 (5%) of adenomas from controls (P < 0.001). In adenomas from LTRs, the mean proliferative activity was higher compared with controls (60.3 +/- 3.2% versus 42.7 +/- 2.8%, P < 0.001), whereas mean apoptotic indices were lower in LTRs (0.29 +/- 0.08% versus 0.39 +/- 0.06%, P = 0.05).


CONCLUSIONS
The presence of JCV in the colorectal mucosa and adenomas from LTRs, in concert with the use of immunosuppressive agents, suggests that JCV may undergo reactivation, and the subsequent TAg protein expression might explain the increased risk of colorectal neoplasia in LTRs.
Selgrad
Michael
M
Department of Internal Medicine, Baylor University Medical Center, Dallas, TX 75246, USA.
Koornstra
Jan Jacob
JJ
Fini
Lucia
L
Blom
Marloes
M
Huang
Rong
R
Devol
Edward B
EB
Boersma-van Ek
Wytske
W
Dijkstra
Gerard
G
Verdonk
Robert C
RC
de Jong
Steven
S
Goel
Ajay
A
Williams
Sharenda L
SL
Meyer
Richard L
RL
Haagsma
Elizabeth B
EB
Ricciardiello
Luigi
L
Boland
C Richard
CR
D000230:Adenocarcinoma / Q000628:therapy / Q000821:virology; D000236:Adenoma / Q000628:therapy / Q000821:virology; D018256:Adenomatous Polyps / Q000628:therapy / Q000821:virology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000032:analysis; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007577:JC Virus / Q000302:isolation & purification* / Q000502:physiology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000821:virology*; D011379:Prognosis; D014412:Tumor Virus Infections / Q000821:virology*; D014775:Virus Activation; D055815:Young Adult
D000957:Antigens, Viral, Tumor; D004279:DNA, Viral